title: Vesicular membrane permeability of monomethylarsonic and dimethylarsinic acids.
abstract: The transmembrane permeability coefficients of the environmentally sensitive arsenicals, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) have been measured for egg phosphatidylcholine large unilamellar vesicles. The determination of the vesicle concentration-independent first-order rate constants for membrane transport and the permeability coefficients were made using an NMR technique employing shift agents. The permeability coefficient of DMA was found to be two orders of magnitude greater than that of MMA. This is attributed to the presence of MMAs extra hydroxyl group. Both species are shown to permeate membranes in the neutral form. Both the temperature dependence and the dependence on cholesterol content were investigated for DMA. The activation energy and the Arrhenius preexponential factor were found to be dependent on the cholesterol content. A marked increase in both parameters was observed up to 20 mol.% cholesterol, with a further, small increase up to 60%. The significance of these results to our understanding of membrane transport is discussed. The importance of using permeability coefficients rather than n-octanol/water partition coefficients in determining bioavailability and bioaccumulation of environmentally sensitive compounds is also discussed.
authors.affiliation: University of British Columbia, Vancouver, Canada.
authors.forename: R G
authors.initials: RG
authors.lastname: Males
authors.forename: J C
authors.initials: JC
authors.lastname: Nelson
authors.forename: P S
authors.initials: PS
authors.lastname: Phillips
authors.forename: W R
authors.initials: WR
authors.lastname: Cullen
authors.forename: F G
authors.initials: FG
authors.lastname: Herring
mesh_terms: D001152:Arsenicals / Q000378:metabolism*; D001682:Biological Availability; D001692:Biological Transport / Q000502:physiology; D002101:Cacodylic Acid / Q000378:metabolism; D002784:Cholesterol / Q000494:pharmacology; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D010539:Permeability; D010713:Phosphatidylcholines / Q000378:metabolism; D013696:Temperature
chemical_list: D001152:Arsenicals; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D002784:Cholesterol; D002101:Cacodylic Acid; C020300:monomethylarsonic acid